Evaluation of a 68Ga-Labeled DOTA-Tetrazine as a PET Alternative to 111In-SPECT Pretargeted Imaging

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The bioorthogonal reaction between a tetrazine and strained trans-cyclooctene (TCO) has garnered success in pretargeted imaging. This reaction was first validated in nuclear imaging using an In-111-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linked bispyridyl tetrazine (Tz) ([In-111]In-DOTA-PEG(11)-Tz) and a TCO functionalized CC49 antibody. Given the initial success of this Tz, it has been paired with TCO functionalized small molecules, diabodies, and affibodies for in vivo pretargeted studies. Furthermore, the single photon emission tomography (SPECT) radionuclide, In-111, has been replaced with the beta-emitter, Lu-177 and alpha-emitter, Pb-212, both yielding the opportunity for targeted radiotherapy. Despite use of the 'universal chelator', DOTA, there is yet to be an analogue suitable for positron emission tomography (PET) using a widely available radionuclide. Here, a Ga-68-labeled variant ([Ga-68]Ga-DOTA-PEG(11)-Tz) was developed and evaluated using two different in vivo pretargeting systems (Aln-TCO and TCO-CC49). Small animal imaging and ex vivo biodistribution studies were performed and revealed target specific uptake of [Ga-68]Ga-DOTA-PEG(11)-Tz in the bone (3.7 %ID/g, knee) in mice pretreated with Aln-TCO and tumor specific uptake (5.8 %ID/g) with TCO-CC49 in mice bearing LS174 xenografts. Given the results of this study, [Ga-68]Ga-DOTA-PEG(11)-Tz can serve as an alternative to [In-111]In-DOTA-PEG(11)-Tz.
Original languageEnglish
Article number463
JournalMolecules
Volume25
Issue number3
Number of pages14
ISSN1420-3049
DOIs
Publication statusPublished - 2020

    Research areas

  • tetrazine ligation, PET, SPECT, gallium-68, indium-11

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